Untargeted metabolomics reveals quinic acid as the kiwifruit component that affects brain activity in mice

Plant-based diets are associated with both physical health and psychological wellbeing. Recent evidence suggests that kiwifruit positively affects cognitive functions and mood, but the bioactive components responsible for this are unknown. In this work, we combined two predictive preclinical models of depression (TST and FST) with untargeted metabolomics to evaluate the antidepressant activity of green kiwifruit in mice and to identify the fruit bioactive phytochemicals responsible for this effect. Mice treated with green kiwifruit juice showed dose-dependent reductions in depressive behavior. Two kiwifruit-derived metabolites - quinic acid and caffeic acid sulfate (the latter formed in mice via metabolism of kiwifruit caffeic acid glucosides) - were detected in mouse serum and brain tissue, suggesting they may confer the observed effects. When administered as pure compounds, quinic acid closely replicated the antidepressant effect of kiwifruit juice, whereas caffeic acid glucoside had little impact. Other fruit metabolites may act synergistically with quinic acid to increase its bioavailability in serum and its absorption into the brain parenchyma. Our approach thus led to the discovery of quinic acid as the kiwifruit metabolite capable of rapidly reaching the mouse brain and exerting an antidepressant effect in synergy with other fruit metabolites.